Block 9 - Disease Processes (2) Flashcards
Define parasite
Protozoa (unicellular)
Helminth (multicellular)
Arthropods (ectoparasites)
Define concomidant immunity
Develop immunity against new infections but cannot get rid of the pathogen that you already have
What do anti-protozoal agents target?
Fast growing and young organisms
via their metabolic pathways
What do anti-helminth agenets target?
Non-growing and adult organisms
via their metabolic pathways
What are the 4 main malaria parasites?
How are they diatinguished?
Plasmodium falciparum, vivax, ovale and malariae
PCR
What is the definite and intermediate malaria host?
Definite: Mosquito (sexual reproduction)
Intermediate: Human (no sexual reproduction)
Explain, in detail, the malaria lifecycle
1) Mosquito injects SPOROZITES
2) Exo-erythrocytic cycle: Sporozites infect the liver cell which ruptures and releases SCIZONTS that rupture to release MEROZOITES
3) Erythrocytic cycle: Merozoites infect cells forming TROPHOZITES then more schizonts which then rupture and infect more cells
4) Trophozites also form GAMETOCYTES which enter the mosqito (macro = F) (micro = M)
5) The gametocytes form an OOKINETE in the stomach, OOCYST in the midgut which released SPOROZITES which go to the salivary glands
What mosquito carries malaria?
The female anapheles mosquito
What are the 3 complications of malaria?
Acodosis (respiratory distress) Severe anaemia Cerebral malaria (unarousable coma related to meningitis, convulsions and hypoglycaemia)
What organism causes African Tyranosomiasis?
What is another name for the disease?
How does the organism cause disease?
Tyranosoma brucei
Sleeping sickness
- Parasite in circulation = no symptoms
- Parasite crosses BBB –> CNS infection and death
What organism causes South American Tyranosomiasis?
What is another name for this disease?
How does the organism enter the body?
How does the organism cause disease?
Tyranosoma cruzi
Chagas disease
Insect bites and faeces enter through a lesion (also congnital, food, blood transfusion)
Acute = no symptoms
Chronic = heart, GI and neurological problems
What transmits Leishmaniasis?
Where does it reside in the body?
What disease does it cause?
Female sandfly
Resides intracellularly often in macrophages
Asymptomatic in the beginning but causes disruption to mucus membranes
What organism causes Toxoplasmosis?
What disease is often caused?
Toxoplasma gondii
Mild lymphadenopathy
Give 2 examples of intestinal protozoans
What disease do they cause?
What do they normally cause?
Entameba histolytica –> Amoebiasis (intestinal and extra retinal infections)
Giardia Lambila –> Giaraiasis (diarrhoea)
Usually non-pathogenic
WHAT ARE THE 6 EXAMPLES OF PROTOZOANS
Malaria African Tyranosomiasis South American Tyranosomiasis Leishmaniasis Toxoplasmosis Intestinal protozoans
How do helminths cause infection?
What causes the problems in a helminth infection?
Infection by larvae/eggs causes problems
Adults are large but do not replicate and do not cause many problems
Give 3 examples of soil transmitted helminths
Ascarls (eggs secreted in faeces and human digest)
Hookworm
Whipworm
What causes Taeniasis infection?
How is it transmitted?
Larval cysts
Contaminated meat
What is another name for Schistomiasis
How is it transmitted?
Where do the helminths reside and when are symptoms caused?
Bilharzia
Spread by water contaminated with urine
Adult worms in blood vessels
Eggs in the bladder and intestine causing symptoms
What is another name for Lymphatic Filriasis
What helminth causes it?
How is it transmitted?
What is the disease mechanism?
Elephantitis
Roundworms
Mosquito
Larvae block the lymphatic system
What is another name for Echinoccocosis?
Where is the adult, egg and larvae?
Hydarid disease
Adult in definite host (animal)
Eggs in faeces
Larval cysts form in the organs
What is the disease process in Dracunculiasis?
What is the treatment?
The worm moves over joints causing pain
Treatment is removal
WHAT ARE THE 6 EXAMPLES OF HELMINTHS?
Soil transmitted Taeniasis Schistomiasis Lymphatic Filriasis Echinoccocosis Dracunculiasis
What mite causes scabies?
The human itch mite
What is another name for:
Tapeworms
Flukes
Roundworms
Tapeworms: Cestodes
Flukes: Trematodes
Roundworms: Nematodes
What is a wood’s lamp used for?
Looks for pigments and bacteria by using UVA light
Fluoresces
What do you look for in the skin? (SCAM)
Size, Shape, Symptoms
Colour
Associated seconday changes
Morphology, Margin
5 things you palpate for in the skin?
Surface, Consistency, Mobility, Tenderness, Temperature
3 clinical features of Lichen Planus
Small bites on the wrist
Nail problems
White scarring on mucus membranes
What is the difference between erythema and purpura?
Erythema: Redness due to inflammation/vasodilation which disappears on pressure
Purpura: Red/purple bleeding into the skin/mucus membranes which doesn’t disappear on pressure
Define auritis
Itching
Define naevus
Localised malformation of tissue
Define ecchymoses
Large patches on the skin
3 causes of hyper-pigmentation
1 cause of de-pigmentation
Pill, pregnancy, drugs
Vitiligo (decreased melanocytes)
What is the treatment of acne?
Antibiotics
Give 4 clinical features of acne
Seborrhoea: increased oil due to androgens turning on sebaceous glands
Comedomes: non-inflammatory
Papules and pustules: inflammatory
Scarring
What are the 3 types of comedomes and their characteristics?
Open: blackhead (large; filled with melanin)
Closed: whitehead (small)
Early-mid-facial (severe)
Give 3 examples of superficial inflamed lesions
Macule: Flat
Papule: Raised and red
Pustule: Raised, red and pus
Give 2 examples of deep inflamed lesions
Nodule: Solid lesion, not always visible
Cyst: Nodule with fluid
Where do you find eczema in INFANTS?
Face and extensors
flexors in children
Give 2 examples of skin findings with atopic eczema
Vesicles and bulla
What causes psoriasis
Hyperproliferation of keratinocytes and inflammatory cell infiltration
5 clinical signs of psoriasis
Plaque: Palpable raised lesion Urticaria: Wheals due to histamine Koebner effect Nail changes Joint problems
8 causes of psoriasis
Genetic, immune, environment
Trauma, infection, drugs, alcohol, stress
2 complications of psoriasis
Erythroderma: A lot of skin affected causing secondary infection, fluid, loss, electroylte imbalance, hypothermia, capillary leak, renal and heart failure
Inflamatory dermatosis: 90% of body affected
Define abscess
Accumulation of pus in the dermis
2 benign skin tumours
Warts
Seborrheic keratoses
3 examples of fungi which infect the skin
Candida, Tinea, Yeast
3 examples of viruses which infect the skin
Herpes zoster, HPV, Herpes simplex
What is the difference in presentation of a BCC and SCC
BCC: Pearly rolled edge with spider veins and a necrotic centre
SCC: Pink and scaly
Where is the most common site for a menaloma in a male and female?
Male: Trunk
Female: Legs
What are the 4 types of melanoma?
Where are they found?
What age do they occur in?
What type of UV exposure causes them?
Superficial spreading: Legs, young, intermittent high intensity UV
Nodular: Trunk, young, intermittent high intensity UV
Lentigo maligna: Face, elderly, long term cumulative UV
Acral lentiginous: palms soles and nail beds, elderly, not related to UV
Define tumour
Swelling
Define neoplasm
Abnormal mass of cells due to poorly regulated proliferation
Define cancer
Malignant tumour/neoplasm
3 characteristcs of the mutations in a cancer cell
They must happen in the genes controlling cell proliferation (tumour suppressor or oncogenes)
Affect a proliferating cell
Accumulate over time
What are the 8 hallmarks of cancer
1) Self sufficiency in growth signals (oncogenes)
2) Insensitivity to antigrowth signals (tumour supressor)
3) Evasion of apoptosis
4) Replicative immortality (telomerase)
5) Sustained angiogenesis
6) Tissue evasion and metastasis
7) Reprogramming of energy metabolism
8) Evasion of host immune defences
What happens in each of the 5 stages of the cell cycle?
G0: Not dividing G1: Replication of cell contents and machinery S: DNA replication G2: Prepare to divide M: Division
What regulates the cell cycle?
cyclin-CDK complexes
What are the 4 cell cycle checkpoints?
G0-G1: Growth factors ensure more cells are needed
G1-S: DNA damage checkpoint, replication machinery triggered and environment and cell checked for readiness
G2-M: DNA replication checkpoint (has it all been replicated), DNA damage checkpoint, mitosis machinergy triggered and environment checked
M-G1: Mitotic spindle assembly checkpoint and chromosomes checked for alignment
Give 4 examples of external signalling mechanisms
Growth factors (activate transcription factors)
Receptors
Signal transduction pathway
What does DNA damage activate
DNA damage activates ATM which can activate
BRACA –> DNA repair
P53 which inhibit CDK complexes
CDK complexes can no longer phosphorylate Rb so DNA synthesis is stopped
Which gene causes cancer- oncogenes or proto-oncogenes?
What do the normal genes do? (2)
Oncogenes cause cancer
Proto-oncogenes code for normal cell regulatory factors e.g. growth factors, transcription factors
How many mutations do you need in oncogenes?
1 mutation
How can gene amplification cause cancer?
The gene coding for oncogenes is amplified
How many mutations do you need in tumour suppressor genes?
Why?
2 mutations
One in each allele
(one inherited and one acquired)
Define the role of a gatekeeper genes
2 examples
Loss of the gene leads to increased proliferation
P53 and Rb
Define the role of a caretaker gene
1 example
Maintain genetic stability e.g. DNA repair
BRACA
Explain how p53 works
DNA damage checkpoint
P53 is degraded if the DNA is normal
ATM phosphorylates P53 if the DNA is damaged –> inhibition of CDK and prevention of Rb synthesising DNA
If the DNA cannot be repaired, P53 –> puma and apoptosis
What instructs Rb to release the transcription factor?
CDK phosphorylates Rb when the cell is instructed to proliferate
What are the 2 viral oncogenes which the HPV virus produces?
What do they do?
E6: Removes p53
E7: Captures Rb
What is the process of cell structure change?
Metaplasia - Dysplasia - Neoplasia
Define parenchyma
Proliferating cells
How does H.pylori cause a reduction in the stomach pH
Produces urease –> CO2 –> ammonia –> decreased pH
Benign and malignant tumour of the surface epithelia
Benign: Papilloma
Malignant: Carcinoma
Benign and malignant tumour of the glandular epithelia
Benign: Adenoma
Malignant: Adenocarcinoma
Benign and malignant tumour of the adipose tissue
Benign: Lipoma
Malignant: Liposarcoma
Benign and malignant tumour of the smooth muscle
Benign: Leiomyoma
Malignant: Leiomyosarcoma
Benign and malignant tumour of the skeletal muscle
Benign: Rhabdomyoma
Malignant: Rhabdomyosarcoma
What are lymphoid malignancies?
Malignancies of the lymphoid lineage of the blood cells
Define choristoma
A tumour arising from a germ layer foreign to the site of the tumour
Define hamartoma
A benign tumour which resembles a neoplasm in its tissue of origin
What can tumours form in veins?
Embolisms
Define anaplasia
What 3 things do cells experience?
Malignant neoplasm made from undifferentiated cells
Pleomorphism (variation in size and shape)
Abnormal nuclear morphology
Atypical mitosis
Define paraneoplastic syndrome
What can it be mistaken for?
Symptoms due to local or distant spread of the tumour
Includes hormone production by tissues
Can be mistaken for metastasis
Define tumour grade
The degree of differentiation
Define menschymal malignancy
Soft tissue malignancy
How is tumour grade assessed?
Tubuleacinar/glandular formation
Nuclear changes (atypical) and pleomorphism
Frequency of mitosis
Each component is graded from 1-3 to give an overall score
Grade 1 = 3-5
Grade 2 = 6-7
Grade 3 = 8-9
Define tumour stage
The extent of spread
How is tumour stage assessed?
T0-T4
N0-N3
M0-M1
Give 5 examples of DNA damage
Pyrimidine dimers (UV) DNA cross-links Base oxidation, hydrolysis and free radicals Single/double strand breaks Replication errors
Explain how biotransformation can cause DNA damage
Biotransformation is the enzymatic process which transforms chemicals to excretory products which can cause DNA damage
e.g. CP450 enzymes add aflatoxin –> damage
What happens in spontaneous deamination?
One base is changed for another
Give 4 methods of DNA repair
Direct reversal
Base/nucleotide excision repair
Mismatch repair
Double strand break repair
What does the direct reversal repair system repair?
How?
Alkylation damage
O-6 methylguanine-DNA methyltransferase (MGMT) ‘picks up’ the alkyl group from the DNA
What does the base excision repair system repair?
How?
Removes damaged bases
DNA glycoslyases remove damaged bases and AP endonuclease repair the gap
What does the double strand break repair system repair?
How?
Ionising radiation damage
End binding, processing and ligation
What cancers can be treated with alkylating agents?
Cancers with decreased MGMT expression
What does the nucleotide excision (mismatch) repair system repair?
How?
DNA damage not recognised by the base excision repair system (bulky lesions)
XP DNA damage complex binds to the DNA
XP helicases separate the DNA
XP endonueleases cut the damage and remove an oligonucleotide fragment along with the damaged base
DNA polymerases repair the fragment
What mutation means that you have a high sensitivity to sunlight?
Defect in the XP proteins
What gene is involved in Familial Adenomatous Polyposis? What class of gene is it? How does it cause cancer?
APC gene
Tumour suppressor - Gatekeeper
APC gene blocks beta catenin (a transcription factor)
APC gene mutated = beta catenin released = proliferation
What gene is involved in Hereditary non polyposis colon cancer? What class of gene is it?
hMSH1 and 2
Tumour suppressor - Caretaker
Genes normally repair replication errors and DNA damage
Mutations cause mutations, expansion of mutated sequences, DNA instability
Which colon cancer affects the right colon?
What is the usual age of onset?
HNPCC
Early
Which colon cancer has an increased cancer risk?
HNPCC
What are the two methods of damaging DNA in radiotherapy?
Indirect action: Photon produces a free radical which attacks the DNA
Direct action: Radiation attacks the DNA
Give an advantage and disadvantage of bradytherapy
Continuous low dose rate –> higher overall rate
Cannot be used if at risk of metastasis
How is external beam radiation given?
Linear accelerator
What does the timing of acute tissue reactions in chemotherapy depend upon?
2 examples
The timing depends on the stage of the cell cycle
Epithelial reactions - heals after treatment
Mucositis - mucosal membrane disruption
What limits the maximum dose of radiotherapy?
How long does it take to develop and how long does it last?
What cells are impacted?
Late tissue reactions
Takes months - years to develop and is permanent
Cells with low turnover rates are affected
Give 6 examples of late tissue reactions
> Xerostomia: dry mouth - dental decay
Skin fibrosis
Soft tissue necrosis: mucus ulcers, vessel and bone damage
Ocular: cataracts, neuropathy
Otolotic: otis media
Nerve tissue damage: spinal cord damage (paraplegia), transverse myelitis, brain necrosis, dementia, Sompolence syndrome (CNS effects)
What cells does acute and long-term toxicity affect?
Acute: Self-limiting damage to normal cells
Long-term: Organ damage
How can chemotherapy cause neutropenic sepsis?
Decrease in WBC, RBC and platelets
Define neoadjuvant and adjuvant in regard to chemotherapy
Neoadjuvant: Pre-surgery
Adjuvant: Post-surgery
What can chemotherapy cause to happen to the: Lung CNS Heart Endocrine
Lung: fibrosis
CNS: dementia
Heart: cardiomyopathy
Endocrine: decreased growth
How can cancer cells build up resistance to cytotoxic drugs?
Increased expression of MDR-1 gene which causes drug efflux
How do cancer cells become resistant to methotrexate?
Decreased sensitivity and binding to the target
Increased permeability of transporters decreases drug accumulation
How do cancer cells become resistant to cisplatin?
Which mechanism is also used for resistance to doxorubicin?
Increased permeability of transporters decreases drug accumulation
Chemicals which trap the drug (doxorubicin)
Increased nucleic acid repair
Who did the tyrosine kinase inhibitors work best in?
People who had a deletion in 19 and a point mutation in 21
Deletion in 19 - the receptor prefers to bind to the drug rather than ATP
How does growth factor binding to EGFR cause cell proliferation?
What is special about these pathways?
P13K –> AKT –> mTOR
RAS –> RAF –> MAP2K
All of these can be inhibited!
What are the receptors called on tumour cells and T cells?
What antibodies overcome this?
Problem with them
Tumour cell: Programmed death receptor ligand 1
T cell: Programmed death receptor 1
PDL-1 and PD-1 antibodies can overcome this (immune checkpoint inhibitors)
Can cause autoimmune issues
Explain how PABP inhibitors can be used as a cancer treatment
Damage to DNA = PABP repairs the damage
Inhibit PABP = no repair and apoptosis
